Viscous or viscoelastic agents used in surgery may perform a number of different functions, including, without limitation, maintenance and support of soft tissue, tissue manipulation, lubrication, tissue protection, and adhesion prevention. It is recognized that the differing rheological properties of these agents necessarily impact their ability to perform these functions, and, as a result, their suitability for certain surgical procedures. See, for example, U.S. Pat. No. 5,273,056, the contents of which are by this reference incorporated herein.
A number of viscous or viscoelastic agents (hereinafter “agents” or “viscoelastics”) are known for ophthalmic surgical use: Viscoat® (Alcon Laboratories, Inc.) which contains sodium hyaluronate and chondroitin sulfate; Provisc® (Alcon), Healon®, Healon® GV, and Healon®5 (Pharmacia Corporation), Amvisc® and Amvisc® Plus (Bausch & Lomb, Inc.), and Vitrax® (Allergan Inc.) all of which contain sodium hyaluronate; and Cellugel® (Alcon) which contains hydroxypropylmethylcellulose (HPMC). All of the foregoing examples of viscoelastics may be used in cataract surgery. They are used by the skilled ophthalmic surgeon for several purposes, including maintenance of the anterior chamber of the eye and protection of ophthalmic tissues during surgery, particularly corneal endothelial cells, and as an aid in manipulating ophthalmic tissues.
While all of the agents described above may be used during cataract surgery, each has certain recognized advantages and disadvantages. Viscoelastics that are dispersive tend to offer better coating and protection of delicate tissues, such as the endothelial lining of the cornea. Cohesive viscoelastics, on the other hand, tend to be “stiffer”, offering an advantage in soft tissue manipulation, e.g., capsulorhexis, but do not coat as well and are prone to accidental or premature aspiration. See, Miyauchi et al., “The Optimal Molecular Weight of Dispersive Type Sodium Hyaluronate for the Reduction of Corneal Endothelial Damage Induced by Sonication, Irrigation, and Aspiration,” Jpn J. Ophthalmol., 45:339-347 (2001). Thus, during phacoemulsification, a less cohesive, i.e. more dispersive, viscoelastic is desired to avoid total evacuation of the anterior chamber and collapse of the corneal dome. See also U.S. Pat. No. 5,273,056, which teaches sequential administration of viscoelastics possessing different rheological properties.
Generally, however, all such agents having sufficient viscosity and pseudoplasticity to be useful in ophthalmic surgery will, if left in the eye at the close of surgery, result in a transient increase in intraocular pressure (“IOP”) known as an “IOP spike.” (See, Obstbaum, Postoperative pressure elevation. A rational approach to its prevention and management, J. Cataract Refractive Surgery 18:1 (1992).) The pressure increase has been attributed to the agent's interference with the normal outflow of aqueous humor through the trabecular meshwork and Schlemm's canal. (See, Berson et al., Obstruction of Aqueous Outflow by Sodium Hyaluronate in Enucleated Human Eyes, Am. J. Ophthalmology, 95:668 (1983); Olivius et al., Intraocular pressure after cataract surgery with Healon®, Am. Intraocular Implant Soc. J. 11:480 (1985); Fry, Postoperative intraocular pressure rises: A comparison of Healon, Amvis, and Viscoat, J. Cataract Refractive Surgery 15:415 (1989).) IOP spikes, depending on their magnitude and duration, can cause significant and/or irreversible damage to susceptible ocular tissues, including, without limitation, the optic nerve.
Consequently, viscoelastics are typically removed from the eye just prior to the close of surgery. The ease with which an agent can be removed from the surgical site, typically by aspiration, has traditionally been considered an important characteristic in the overall assessment of the agent's usefulness in cataract surgery. By removing the agent before the close of surgery, the surgeon hopes to minimize or avoid any significant IOP spike. Unfortunately, however, removal of agents which are relatively dispersive (as opposed to cohesive) or which adhere to the ocular tissue is often difficult and may cause additional trauma to the eye.
Alternatives to removing the viscoelastic have been suggested. For example, exogenous dilution of the viscoelastic has been suggested to alleviate IOP spikes. See U.S. Pat. No. 4,328,803. Depending, however, on the particular viscoelastic and the surgical technique employed, IOP spike may still be a problem. More recently, it has been suggested that the administration of degradative agents to break down conventional viscoelastics in the eye can reduce or avoid the occurrence of IOP spikes. See, e.g., U.S. Pat. No. 5,792,103. Such an approach requires not only the administration of an enzymatic agent into the eye, the biocompatability of which must be assured, but also means for adequately mixing the two agents via a special apparatus. Such approaches, which could leave residual material in the eye and thereby result in an IOP spike, have not been adopted by the ophthalmic community, which prefers to aspirate the viscoelastic from the eye at the close of surgery.
There is, therefore, a need for an improved means for reducing or avoiding IOP spikes associated with the use of conventional viscous or viscoelastic agents in ophthalmic surgery, especially cataract surgery. More specifically, a need exists for an improved methodology that will lend to traditional, hyaluronate-based viscoelastics variable rheological properties that can improve their performance during surgery and facilitate their removal at the end of surgery is recognized. The commonly assigned parent application to the present application, U.S. patent application Ser. No. 10/380,135, the entire contents of which are by this reference incorporated herein, is directed to an invention to serve this need. More specifically, that invention involves supplementing the irrigating solution used in such surgeries with relatively low molecular weight polymers that, when mixed with a cohesive hyaluronate-based viscoelastic, have the effect of modifying the rheological properties at the interface with the irrigating solution, and particularly the cohesiveness of such viscoelastic, to improve its performance in surgery. Irrigating solutions for use in surgery and particularly ophthalmic surgery are well known. See, e.g. commonly assigned U.S. Pat. No. 4,443,432. It has also been suggested that viscous or viscoelastomeric substances may be added to irrigating solutions to reduce cell loss. See commonly assigned U.S. Pat. No. 5,409,904, the contents of which are by this reference incorporated herein.
The use of viscoelastic agents in joint therapy is also known in the art. Viscoelastic joint therapy involves the intra-articular application of commercially available sodium hyaluronate viscoelastic materials such as HYLAN G-F 20, SYNVISC, HYALGAN, ARTZ, etc. The sodium hyaluronate substance is thought to affect the rheology of the synovial fluid, producing an almost immediate sensation of free movement and a marked reduction of pain in patients suffering from chondromalacia and/or arthritis, and particularly osteoarthritis. Chondroitin sulfate is also known to be useful in the treatment of diseased or traumatized joints. See U.S. Pat. No. 5,498,606. Viscoelastic materials such as sodium hyaluronate have also been used in cosmetic and reconstructive surgery to treat wrinkles and add fullness. Further, viscoelastic agents, for example sodium hyaluronate and chondroitin sulfate, have been used as a packing material for use in middle ear surgery, as described in commonly assigned U.S. Pat. No. 6,632,423, the contents of which are incorporated herein. However, for all applications in which sodium hyaluronate is subject to irrigation, whether exogenous or endogenous, there will be a dilution effect and a resulting loss of the desired viscosity, with a corresponding reduction in the time a treatment will remain effective (e.g., in reduction in pain viscoelastic joint therapy).
There is a need, therefore, for a viscoelastic substance that is less susceptible to dilution and viscosity loss than prior art viscoelastic substances.